1,3-Dithiolane, 2-methoxy

The pivotal step in this sequence is an electrophilic substitution on indole. Although the use of l,3-dithian-2-yl carbanions is well documented, it has been shown only recently that 1,3-dithian-2-yl carbenium ions can be used in a Priedel-Crafts type reaction. This was accomplished initially using 2-methoxy-l,3-dithiane [1,3-Dithiane, 2-methoxy-] or 2-metlioxy-l,3-dithiolane [1,3-Dithiolane, 2-methoxy-] and titanium tetrachloride [Titanate(l —), tetrachloro-] as the Lewis acid catalyst.9 2-Substituted lysergic acid derivatives and 3-substituted indoles have been prepared under these conditions, but the method is limited in scope by the difficulties of preparing substituted 2-methoxy-1,3-dithianes. l,3-Dithian-2-yl carbenium ions have also been prepared by protonation of ketene dithioacetals with trifluoroacetic acid,10 but this reaction cannot be used to introduce 1,3-dithiane moieties into indole. 

Methane Difluoro-(4-methoxy-phenyl)-phenyl- ElOb, 215 (2-Ar - 2-Ar — 1,3-dithiolane + HF)... 

An excellent method for the preparation of gem-difluoro compounds from aldehydes and ketones consists of conversion of the carbonyl compound to the corresponding 1,3-dithiolane followed by treatment with two equivalents of l,3-dibromo-5,5-dimethylhydantoin (DBH) and pyridinium poly(hydrogen fluoride) (HF-pyridine) in methylene chloride. Attempted extension of this procedure to 7-methoxy-2,2-dimethyl-4-chromanone, however, gave only the dihydro- 1,4-dithiin derivative 1 in 78% yield. This transformation, which proceeded in excellent yield with a variety of 4-chromanones, was found to require only the DBH (i.e. fluoride ion played no role). 

In a new reaction of the Friedel-Crafts type, using 2-methoxy-l,3-dithiolane and a weak Lewis acid such as TiCl4 the ester 45 could be obtained (45). This compound was either hydrolyzed to the 2-formyl derivative or desulfurized with Raney nickel to the 2-methyl compound. 

The extension of the use of lactams to include indolin-2-ones provides a Vilsmeier-type methodology for the construction of biindolyl systems, which are of considerable current interest.37,39-43 In this situation, the initially formed imines are indolenines, which readily isomerize to the related 2-indolyl derivatives.43 In view of our general interest in activated indoles, as well as a specific interest in continuing to synthesize structures containing indoles directly linked to each other, we investigated not only reactions with indolinone itself but also with substituted derivatives. These were variously methoxy-substituted at C-4 and C-6, and in some cases substituted also at C-3 with methyl, phenyl, or dithiolan groups. 

The preparation of 2-methoxy-l,3-dithiolane (292) is based on the reaction of dichloromethyl methyl ether with the disodium salt of ethanedithiol in acetonitrile (72HCA75). 

The 1,3-dithiolane 1,3-dioxide 365 was also investigated in the Diels-Alder reaction with a range of simple dienes (cyclopentadiene, 1-methoxybutadiene, l-methoxy-3-trimethylsilyloxybutadiene, furan) <1995JOC4962, 1998J(P1)2771> and 1,3-dipolar cycloadditions with A - /t-butyl-(7-phenyl nitrone <1998JOC3481> or 3-oxidopyr-idinium betaines <20030BC1884>. 

Reaction of 1,2-ethanedithiol with dichloromethyl methylether in the presence of sodium results in the formation of the 2-methoxy-l,3-dithiolane (360) (Scheme 65) <72HCA75>, whereas its reaction with phosgene yielded the l,3-dithiolan-2-one (361) <41RTC453>. 

Bis-[ethylthio -methoxy-methan Bis-[ethylthio]-ethoxy-methan Methoxy-methylthio-phenylthio-methan 2-Methoxy-l, 3-dithiolan 2-Methoxy-1,3-dithian 2-Isopropyloxy-l, 3-dithian... 

The two methoxy groups in amide acetals can be replaced by a dithiol forming 1,3-dithiolanes (34),... 

Unusual pyronotropane tropane alkaloids have been fotmd in the family Proteaceae. Tropine and pseudotropine esters of benzoic acid have been isolated from the family Euphorbiaceae. Novel dithiolane esters, along with tropine esters of acetic, propionic, n-butyric, isobutyric, isovaleric, and benzoic acids have been fotmd in the Rhizophoraceae. Calystegines, as well as a 3-hydroxybenzoate ester, have been fotmd in Brassicaceae. The calystegines have been used as chemotaxonomic markers in the Convolvulaceae family [20]. Tropine esters with methoxy-substituted benzoic acids are also characteristic for the later family. 

Position 2 of the ergoline skeleton is highly suitable for synthetic modification of EA by both electrophilic and radical substitution. Many modifications have been reviewed by Rutschmann and Stadler (1978) chlorination, bromination and iodination, nitration and reduction of nitro derivatives to amino derivatives and reaction with 2-methoxy-l, 3-dithiolane affording an intermediate which can be desulfurised to a 2-methyl derivative. Troxler and Hofmann (1959) described the oxidation of lysergic acid diethylamide (LSD) to 2-oxo-3-hydroxy-2, 3-dihydrolysergic acid diethylamide. 

Ethano-bridged phthalate ester 56 was obtained by the DA reaction in good yield and was converted to the BCOD-fiised triester 57a, the t-butyl ester group of which was removed by treatment with TFA (Scheme 15.10) [63]. The DA reaction of tosylacetylene (5a) and 2-methoxy-l,3-cyclohexadiene proceeded smoothly to afford a diastereomeric mixture (5 1) of bicyclo[2.2.2]octenone 58 in 73% yield after hydrolysis by silica gel [64]. Diastereomeric 58 was quantitatively converted to dithiolane, which was subject to the ring expansion reaction with tellurium tetrachloride [65]. Dihydro-1,4-dithiin 59 was obtained in 74% yield. The Barton-Zard reaction of 59 with ethyl isocyanoacetate afforded pyrrole-carboxylate 60a (77% yield), which was transformed to both a-hydroxymethylpyrrole 60b and a-firee pyrrole 60c in good yields. 

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